System for detecting biological reactions on a substrate using waveguides and nanopores

Abstract

A device for fluorescence-based detection of at least one polymer, the device including at least one container, at least one light source, at least one detector and at least one optical element, the container including a nanopore membrane and a waveguide layer, the nanopore membrane including at least one nanopore and the waveguide layer including at least one opening, the light source optically coupled with the waveguide layer and for generating at least one light beam for illuminating the polymer, the detector for detecting at least one emission emitted from the illuminated polymer and the optical element for entering the light beam into the waveguide layer, the opening being positioned substantially in line with the nanopore, the polymer being illuminated by the light beam propagating through the waveguide layer through the opening and the illuminated polymer emitting the emission as it passes through the nanopore and the opening.

1 . A device for fluorescence-based detection of at least one polymer, the device comprising:
 at least one container comprising:
 a nanopore membrane, comprising at least one nanopore; and 
 a waveguide layer, comprising at least one first opening, 
   at least one light source, optically coupled with said waveguide layer, for generating at least one light beam for illuminating said at least one polymer;   at least one detector, for detecting at least one emission emitted from said illuminated at least one polymer; and   at least one first optical element, for entering said at least one light beam into said waveguide layer,   wherein said at least one first opening is positioned substantially in line with said at least one nanopore;   wherein said at least one polymer is placed within a solution within said at least one container;   wherein said at least one polymer is illuminated by said at least one light beam propagating through said waveguide layer through said at least one first opening; and   wherein said illuminated at least one polymer emits said at least one emission as it passes through said at least one nanopore and said at least one first opening.   
     
     
         2 . The device for fluorescence-based detection according to  claim 1 , wherein said waveguide layer is a dielectric film positioned adjacent to said nanopore membrane. 
     
     
         3 . The device for fluorescence-based detection according to  claim 2 , wherein at least one end of said dielectric film bordering said at least one first opening has a shape selected from the list consisting of:
 a square end; and   a curved end.   
     
     
         4 . The device for fluorescence-based detection according to  claim 1 , wherein said waveguide layer is a dielectric film positioned on one side of said nanopore membrane;
 wherein said device further comprises an electromagnetic (EM) concentration layer positioned on the other side of said nanopore membrane;   wherein said EM concentration layer comprises at least one second opening, also positioned in line with said at least one nanopore; and   wherein said illuminated at least one polymer emits said at least one emission as it also passes through said at least one second opening.   
     
     
         5 . The device for fluorescence-based detection according to  claim 4 , wherein said EM concentration layer is a metal film. 
     
     
         6 . The device for fluorescence-based detection according to  claim 1 , wherein said waveguide layer is a dielectric film positioned on one side of said nanopore membrane;
 wherein said device further comprises a dielectric interference filter positioned on the other side of said nanopore membrane; and   wherein said dielectric interference filter comprises at least one second opening, also positioned in line with said at least one nanopore.   
     
     
         7 . The device for fluorescence-based detection according to  claim 1 , wherein said waveguide layer is a metal film positioned adjacent to said nanopore membrane having a waveguide etched into said metal film. 
     
     
         8 . The device for fluorescence-based detection according to  claim 7 , wherein said waveguide etched into said metal film is positioned over said at least one first opening. 
     
     
         9 . The device for fluorescence-based detection according to  claim 1 , wherein said at least one light source is embedded in said at least one container; and
 wherein said at least one first optical element is positioned inside said waveguide layer, for directing said at least one light beam emitted from said at least one light source into said waveguide layer.   
     
     
         10 . The device for fluorescence-based detection according to  claim 9 , wherein said at least one first optical element is selected from the list consisting of:
 a sub-wavelength structure;   a mirror; and   a prism.   
     
     
         11 . The device for fluorescence-based detection according to  claim 1 , wherein said at least one light source is positioned outside said at least one container and adjacent to said waveguide layer;
 wherein said at least one first optical element is a collimating lens, positioned between said at least one light source and an entrance to said waveguide layer; and   wherein said collimating lens focuses said at least one light beam emitted from said at least one light source into said waveguide layer.   
     
     
         12 . The device for fluorescence-based detection according to  claim 1 , wherein said at least one light source is positioned at an angle to said at least one container;
 wherein said at least one first optical element is a sub-wavelength deformation zone within said waveguide layer; and   wherein said sub-wavelength deformation zone focuses said at least one light beam emitted from said at least one light source into said waveguide layer.   
     
     
         13 . The device for fluorescence-based detection according to  claim 1 , further comprising an analyzer, coupled with said at least one detector, for analyzing said at least one emission. 
     
     
         14 . The device for fluorescence-based detection according to  claim 1 , further comprising a second optical element, positioned between said at least one detector and said at least one container, for directing said at least one emission towards said at least one detector. 
     
     
         15 . The device for fluorescence-based detection according to  claim 1 , further comprising at least one respective detector filter, positioned between said at least one detector and said container. 
     
     
         16 . The device for fluorescence-based detection according to  claim 1 , wherein a wavelength of said at least one light beam is between 400 and 850 nanometers. 
     
     
         17 . The device for fluorescence-based detection according to  claim 1 , wherein said solution is an ionic solution. 
     
     
         18 . The device for fluorescence-based detection according to  claim 1 , wherein said solution comprises a concentration gradient. 
     
     
         19 . The device for fluorescence-based detection according to  claim 1 , wherein said at least one polymer is selected from the list consisting of:
 an organic compound;   an inorganic compound;   a protein;   a polypeptide;   DNA;   RNA; and   a lipid.   
     
     
         20 . The device for fluorescence-based detection according to  claim 1 , wherein said waveguide layer is made from a material selected from the list consisting of:
 SiO 2      TiO 2 ;   Ta 2 O 5 ;   Nb 2 O 5 ;   Si 3 N 4 ;   Al 2 O 3 ;   SiN x ;   poly(methyl methacrylate) (PMMA); and   polydimethylsiloxane (PDMS).   
     
     
         21 . The device for fluorescence-based detection according to  claim 1 , wherein said nanopore membrane is made from a material selected from the list consisting of:
 SiN x ; and   silicon dioxide (SiO 2 ).   
     
     
         22 . The device for fluorescence-based detection according to  claim 1 , wherein said nanopore membrane and said waveguide layer are made from the same material and form a monolithic structure; and
 wherein said nanopore membrane and said waveguide layer have a relative positioning selected from the list consisting of:
 said nanopore membrane being positioned above said waveguide layer in said monolithic structure; and 
 said nanopore membrane being positioned below said waveguide layer in said monolithic structure. 
   
     
     
         23 . The device for fluorescence-based detection according to  claim 22 , wherein said device further comprises an electromagnetic (EM) concentration layer positioned adjacent to said monolithic structure, said EM concentration layer having a relative positioning to said monolithic structure selected from the list consisting of:
 said EM concentration layer being positioned above said monolithic structure; and   said EM concentration layer being positioned below said monolithic structure.   
     
     
         24 .- 69 . (canceled) 
     
     
         70 . A device for fluorescence-based detection of at least one polymer, the device comprising:
 at least one container comprising:
 a nanopore membrane, comprising at least one nanopore; and 
 a waveguide layer, comprising at least one first opening, 
   at least one light source, optically coupled with said waveguide layer, for generating at least one light beam for illuminating said at least one polymer;   at least one detector, for detecting at least one emission emitted from said illuminated at least one polymer;   at least one first optical element, for entering said at least one light beam into said waveguide layer; and   at least one second optical element, positioned between said at least one detector and said at least one container, for focusing said at least one emission onto said at least one detector,   wherein said at least one first opening is positioned substantially in line with said at least one nanopore;   wherein said at least one polymer is placed within a solution within said at least one container;   wherein said at least one polymer is illuminated by said at least one light beam propagating through said waveguide layer through said at least one first opening;   wherein said illuminated at least one polymer emits said at least one emission as it passes through said at least one nanopore and said at least one first opening; and   wherein said at least one emission is detected by said at least one detector by means of free-space propagation.   
     
     
         71 . The device for fluorescence-based detection according to  claim 70 , wherein said waveguide layer is a dielectric film positioned on one side of said nanopore membrane;
 wherein said device further comprises an electromagnetic (EM) concentration layer positioned on the other side of said nanopore membrane;   wherein said EM concentration layer comprises at least one second opening, also positioned in line with said at least one nanopore; and   wherein said illuminated at least one polymer emits said at least one emission as it also passes through said at least one second opening.   
     
     
         72 . The device for fluorescence-based detection according to  claim 70 , wherein said at least one light source is embedded in said at least one container; and
 wherein said at least one first optical element is positioned inside said waveguide layer, for directing said at least one light beam emitted from said at least one light source into said waveguide layer.   
     
     
         73 . The device for fluorescence-based detection according to  claim 72 , wherein said at least one first optical element is selected from the list consisting of:
 a sub-wavelength structure;   a mirror; and   a prism.   
     
     
         74 . The device for fluorescence-based detection according to  claim 70 , wherein said at least one second optical element is selected from the list consisting of:
 a microscope lens;   a collimating lens;   a lens; and   an optical coupler.   
     
     
         75 . The device for fluorescence-based detection according to  claim 70 , wherein said at least one light source is positioned outside said at least one container and adjacent to said waveguide layer;
 wherein said at least one first optical element is a collimating lens, positioned between said at least one light source and an entrance to said waveguide layer; and   wherein said collimating lens focuses said at least one light beam emitted from said at least one light source into said waveguide layer.   
     
     
         76 . The device for fluorescence-based detection according to  claim 70 , further comprising at least one respective detector filter, positioned between said at least one detector and said container.